This multi-year study found that the addition of a molecule called Interleukin-15 effectively boosts the effects of a vaccine derived from the DNA of simian HIV. The study illustrates that DNA vaccine effectiveness can be improved by the inclusion of specific immune adjuvants, or helpers.

The findings are published in last week's online edition of the Proceedings of the National Academy of Sciences.

DNA vaccine technology has great promise for the development of vaccines and immune therapeutics for a variety of infectious diseases and cancers, says senior author David B. Weiner, PhD, Professor of Pathology and Laboratory Medicine at Penn. While previous studies have established that the technology can induce immune responses safely, improving the immune potency of this platform is critical for further development in humans.

The research builds on previous work aimed at engineering a more potent immune response to SHIV DNA vaccine technology. Mouse model studies previously showed that the cytokine IL-15 -- a substance that can improve the body's natural response to infection and disease -- helps better immune responses and protection, while this study mirrors those findings in a larger, non-human primate species.

In this study, the group of macaques that was injected with the vaccine containing a loop of DNA enabling them to make IL-15 developed no signs of AIDS-like symptoms when exposed to live SHIV, compared to four animals in the control group that received only the DNA vaccine. The modified vaccine appeared to help suppress viral replication among the IL-15 group.

Next, Weiner's team will study the protected macaques to determine the actual mechanism of their protection, and seek out any pockets of the virus that may be hiding in specific immune compartments. The approach will also be tested for safety and immunogenicity in humans through the HIV Vaccine Trials Network.

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The researchers have now shown that the same four factors can generate iPS cells from fibroblasts taken from human skin. From about 50,000 transfected human cells, we obtained approximately 10 iPS cell clones, Yamanaka said. This efficiency may sound very low, but it means that from one experiment, with a single ten centimeter dish, you can get multiple iPS cell lines.

The iPS cells were indistinguishable from embryonic stem cells in terms of their appearance and behavior in cell culture, they found. They also express genetic markers that are used by scientists to identify embryonic stem cells. Human embryonic stem cells and iPS cells display similar patterns of global gene activity.

They showed that the converted human cells could differentiate to form three germ layers in cell culture. Those primary germ layers in embryos eventually give rise to all the body's tissues and organs. They further showed that the human iPS cells could give rise to neurons using a method earlier demonstrated for human embryonic stem cells. The iPS cells could also be made to produce cardiac muscle cells, they found. Indeed, after 12 days of differentiation, clumps of cells in the laboratory dishes started beating.

The human iPS cells injected under the skin of mice produced tumors after nine weeks. Those tumors contained various tissues including gut-like epithelial tissue, striated muscle, cartilage and neural tissue. They finally showed that iPS cells can also be generated in the same way from other human cells.

We should now be able to generate patient- and disease-specific iPS cells, and then make various cells, such as cardiac cells, liver cells and neural cells, Yamanaka said. These cells should be extremely useful in understanding disease mechanisms and screening effective and safe drugs. If we can overcome safety issues, we may be able to use human iPS cells in cell transplantation therapies.

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